Mechanism of Action
Nitrate: Nicorandil stimulates guanylate cyclase to increase formation of cyclic GMP (cGMP). cGMP activates protein kinase G (PKG) which phosphorylates and inhibits GTPase RhoA and decreases Rho-kinase activity]. Reduced Rho-kinase activity permits an increase in myosin phosphatase activity, decreasing the calcium sensitivity of the smooth muscle. PKG also activates the sarcolemma calcium pump to remove activating calcium. PKG acts on K+ channels to promote K+ efflux and the ensuing hyperpolarization inhibits voltage-gated calcium channels . Overall, this leads to relaxation of the smooth muscle and coronary vasodilation.
K+ATP channel opener: Nicorandil activates K+ATP channel, causing K+ efflux. This hyperpolarizes the cell, which inactivates voltage-gated calcium channels and reduces free intracellular Ca2+.
The effect of nicorandil as a vasodilator is mainly attributed to its nitrate property. Yet, nicorandil is effective in cases where nitrates, such as nitroglycerine, are not effective. Studies show that this is due to its K+ATP channel agonist action which causes pharmacological preconditioning and provides cardioprotective effects against ischemia. Nicorandil activates K+ATP channels in the mitochondria of the myocardium, which appears to relay the cardioprotective effects, although the mechanism is still unclear.
Read more about this topic: Nicorandil
Famous quotes containing the words mechanism of, mechanism and/or action:
“A mechanism of some kind stands between us and almost every act of our lives.”
—Sarah Patton Boyle, U.S. civil rights activist and author. The Desegregated Heart, part 3, ch. 2 (1962)
“I’ve never known a Philadelphian who wasn’t a downright “character;” possibly a defense mechanism resulting from the dullness of their native habitat.”
—Anita Loos (1888–1981)
“We have seen the city; it is the gibbous
Mirrored eye of an insect. All things happen
On its balcony and are resumed within,
But the action is the cold, syrupy flow
Of a pageant.”
—John Ashbery (b. 1927)